Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000037990 | SCV000061656 | uncertain significance | not specified | 2012-11-05 | criteria provided, single submitter | clinical testing | The Arg425Gln variant in DSP has not been reported in the literature nor previou sly identified by our laboratory. This variant has also not been identified in l arge and broad European American and African American populations by the NHLBI E xome Sequencing Project (http://evs.gs.washington.edu/EVS). Computational analys es (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and S IFT) do not provide strong support for or against an impact to the protein. Addi tional information is needed to fully assess the clinical significance of the Ar g425Gln variant. |
| Ambry Genetics | RCV000253534 | SCV000320626 | uncertain significance | Cardiovascular phenotype | 2015-12-14 | criteria provided, single submitter | clinical testing | The p.R425Q variant (also known as c.1274G>A), located in coding exon 11 of the DSP gene, results from a G to A substitution at nucleotide position 1274. The arginine at codon 425 is replaced by glutamine, an amino acid with highly similar properties. This variant was previously reported in the& SNPDatabase as rs397516916. Based on data from ExAC, the A llele was reported in 3 of 121374 (0.002%) total alleles (Exome Aggregation Consortium (ExAC), Cambridge, MA (URL: http://exac.broadinstitute.org) [Accessed December 7, 2015]). This variant was not reported in population based cohorts in the following databases: NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
| Color Diagnostics, |
RCV001177317 | SCV001341511 | uncertain significance | Cardiomyopathy | 2022-12-12 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with glutamine at codon 425 of the DSP protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 6/251266 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Fulgent Genetics, |
RCV002496606 | SCV002785365 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8; Lethal acantholytic epidermolysis bullosa; Woolly hair-skin fragility syndrome; Keratosis palmoplantaris striata 2; Cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis | 2021-08-20 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002513492 | SCV003321345 | likely benign | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2023-12-16 | criteria provided, single submitter | clinical testing |